Haemophilia A is an X chromosome-linked recessive disorder resulting in defective or deficient Factor VIII molecules, which, in its severe form, is a life-threatening and crippling haemorrhagic disease.
Infusion of homologous Factor VIII to patients with severe haemophilia A results, in 25% of the cases, in the emergence of anti-Factor VIII allo-antibodies (Ehrenforth, S., Kreuz, W., Scharrer, I., Linde, R., Funk, M., Güngör, T., Krackhardt, B. and Komhuber, B., (<<Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs>>, Lancet, 1992, 339: 594-598), that inhibit Factor VIII procoagulant activity by steric hindrance of the interaction of Factor VIII either with stabilising molecules (Saenko, E. L., Shima, M., Rajalakshmi, K. J. and Scandella, D., <<A role for the C2 domain of factor VIII in binding to von Willebrand factor>>, J. Biol. Chem., 1994, 269: 11601-11605; and Saenko, E. L., Shima, M., Gilbert, G. E., and Scandella, D., <<Slowed release of thrombin-cleaved factor VIII from von Willebrand factor by a monoclonal and a human antibody is a novel mechanism for factor VIII inhibition>>, J. Biol. Chem., 1996, 271: 27424-27431), with molecules essential for its activity (Arai, M., Scandella, D., and Hoyer, L. W., <21 Molecular basis of factor VIII inhibition by human antibodies: Antibodies that bind to the factor VIII light chain prevent the interaction offactor VIII with phospholipid>>, J. Clin. Invest., 1989, 83:1978-1984; and Zhong, D., Saenko, E. L., Shima, M., Felch, M. and Scandella, D., <<Some human inhibitor antibodies interfere with factor VIII binding to Factor IX>>, Blood, 1998, 92: 136-142), or with activating molecules (Lubahn, B. C., Ware, J., Stafford, D. W., and Reiser, H. M., <<Identification of a FVIII epitope recognized by a human hemophilic inhibitor>>, Blood, 1989, 73: 497-499; and Neuenschwander, P. F., and Jesty, J., <<Thrombin-activated and factor Xa-activated human factor VIII: differences in cofactor activity and decay rate>>, Arc. Biochem. Biophys., 1992, 296: 426-434).